1. Field of the Invention
The present invention concerns the synthesis of soluble forms of melanin and their composition, and methods of using such compositions to provide a naturally-appearing tan to mammalian skin and hair and to provide a sun-screen, to treat post-inflammatory hypo- and hyperpigmentation, to tint glass and plastic, and to protect industrial materials against ultraviolet damage.
2. Background Information
In biology, melanins are heteropolymers consisting of L-dopa and its enzymatic derivatives. They are ubiquitous in living organisms and are produced throughout the zoological and botanical phyla. In mammalian skin, melanins are produced through enzymatic processes in specialized cells known as "melanocytes". Melanins are the pigments of mammalian skin and hair.
Mammalian melanins are highly insoluble and can be dissolved (solubilized) only through non-physiological treatments such as boiling in strong alkali, or through the use of strong oxidants such as hydrogen peroxide. Tyrosinase, a key enzyme in the melanin biosynthetic pathway, can catalyze the formation of melanin in a test tube using L-tyrosine, L-dopa or 5',6'-dihydroxyindole as substrates, however, the product is an insoluble precipitate as described above.
Ito, "Reexamination of the Structure of Eumelanin", Biochimica et Biophysica Acta, 883, 155-161, 1986, mentions natural melanin may be a polymer of 5,6-dihydroxyindole and 5,6-dihydroxyindole-2-carboxylic acid. Ito, however, does not teach or suggest combining these chemicals to form melanin.
Ito and Nicol, "Isolation of Oligimers of 5,6-Dihydroxyindole-2-carboxylic Acid from the Eye of the Catfish", Biochemical Journal, 143, 207-217, 1974, mention that oligimers of 5,6-dihydroxyindole-2-carboxylic acid exist in nature, for example in the tapetum lucidum of the sea catfish (Arius felis). Ito and Nicol, however do not teach or suggest that these structures could be used as a form of soluble melanin.
Palumbo, d'Ischia, Misuraca, and Prota, "Effect of metal ions on the rearrangement of dopachrome", Biochimica et Biophysica Acta, 925, 203-209, 1987, mention that the metal ions Cu.sup.2+, Ni.sup.2+, and Co.sup.2+ are effective in inducing the non-decarboxylative rearrangement of dopachrome at physiological pH values, leading mainly to the formation of 15,6-dihydroxyindole-2-carboxylic acid. They suggest that when considered in the light of the known metal accumulation in pigmented tissues, their results provide a new entry into the regulatory mechanisms involved in the biosynthesis of melanin. Palumbo et al, however, do not teach or suggest that such metal ions could be used to affect the color or formation of soluble melanin. Likewise, Leonard, Townsend, and King, "Function of Dopachrome Oxidoreductase and Metal Ions in Dopachrome Conversion in the Eumelanin Pathway", Biochemistry, 27 6156-6159, 1988, present similar results to those of Palumbo et al regarding metal ions and the formation of 5,6-dihydroxyindole-2-carboxylic acid from dopachrome. Like Palumbo et al, Leonard et al also do not teach or suggest that such metal ions could be used to affect the color for formation of soluble melanin.
Many reports exist exploring the role of sulfhydryl compounds such as cysteine or glutathione in determining the red or yellow colors in melanin (see review by Pawelek and Korner, "The Biosynthesis of Mammalian Melanin", American Scientist, 70, 136-145, 1982). However these reports do not teach or suggest that said sulfhydryl compounds could be used to influence the colors of soluble melanins.
It would be of commercial value to have forms of melanin which are soluble at physiological pH and temperature. Such melanins could be applied evenly to mammalian skin and hair in appropriate vehicles without any of the caustic side-effects arising from the harsh reagents needed to solubilize precipitated melanins.
Such solubilized melanins could impart a naturally-appearing tan to mammalian skin and hair. Solubilized melanins would also be effective as sun-screens, since melanins are the chemicals in the skin which absorb ultraviolet radiation and thus provide protection from its harmful effects, such as premature skin aging and the occurrence of skin cancers.
Such solubilized melanins would be effective to treat post-inflammatory hypo and hyper-pigmentation due to eczema, acne, trauma, burns and psoriasis. Also, as a cover-up for vitiligo and other disorders of hypopigmentation, soluble melanins would be quite effective.
Since melanins absorb light throughout the ultraviolet and visible spectra, solubilized melanins would also be effective as glass or plastic tinting agents for eye glasses, contact lenses, car windows, house windows, office buildings, etc.
Likewise, by absorbing in the ultraviolet range, solubilized melanins would be effective agents to protect industrial materials against damage from ultraviolet radiation. By "industrial material" or "industrial product" is meant, for example, truck and car tires, paints, laminating materials, plastics, synthetic resins, and fabrics, particularly fabrics containing nylon, and like materials or products. It is well known that the rate of deterioration of paints, wood, plastics and rubber is dramatically increased by exposure to ultraviolet radiation.